The mammalian hematopoietic system comprises a number of cell types that mediate cellular immunity. While being vital to good health in a mammalian organism, dysregulation of the complex immunological systems has been implicated to play a role in a number of pathological diseases and disorders. In addition, there are instances, such as in organ transplantation, where even normal operation of the immunological system can be disadvantageous and have unwanted consequences.
One example of a disease state in a mammal in which the immunological system is thought to play a role is asthma. A population of eosinophils isolated from peripheral blood from normal individuals contains about 5% surviving cells after 3 days of culture. In contrast, cultures of eosinophils isolated from asthmatic individuals contain about 95% surviving cells after 3 days. That this difference is important in the etiology of asthma in humans is supported by work in human and mouse asthma models, where asthma can be induced by injecting the animal with allergen followed by inhalation challenge with that allergen. Significantly, asthma does not result when this protocol is used in mice that lack eosinophils. A role in asthma for eosinophils is further indicated by certain physiologic properties of eosinophils; for example, these cells can release vasoactive materials and cytokines and can lead to scarring of lung tissues. The effects of asthma may be reduced or eliminated by eliminating or reducing eosinophil populations in lungs in asthma patients.
Thus, there is a need in the art for clinically effective compounds and pharmaceutical agents that can inhibit or reduce eosinophil survival or persistence in the lungs of patients who have disorders, such as asthma, that are associated with increased eosinophil activation and accumulation. Similarly, there is a need in the art for more effective methods for treating tissue and organ transplant recipients, to reduce the vigor and persistence of a transplant recipient's immunologic rejection of donor tissues and organs.